沙美特罗未能抑制血小板活化因子诱导的循环白细胞反应和支气管收缩。

Failure of salmeterol to inhibit circulating white cell responses and bronchoconstriction induced by platelet activating factor.

作者信息

Spring J, Johnston S R, Seale J, Ind P W

机构信息

Department of Medicine, Royal Postgraduate Medical School, Hammersmith Hospital, London.

出版信息

Thorax. 1992 Nov;47(11):948-51. doi: 10.1136/thx.47.11.948.

DOI:10.1136/thx.47.11.948

PMID:1361250

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC464105/

Abstract

BACKGROUND

Platelet activating factor (PAF) is a potent mediator of inflammation. Inhalation of PAF causes acute bronchoconstriction and a transient fall in white blood cell count in humans. Salmeterol inhibits pulmonary inflammation induced by PAF in guinea pigs.

METHODS

The effect of salmeterol on effects induced by PAF was investigated in eight normal subjects who inhaled salmeterol (50 micrograms) twice daily or a matched placebo for one week before challenge with PAF. Blood samples were taken from a forearm catheter for total white cell and neutrophil counts before and for 30 minutes after administration of PAF (48 micrograms) through a Mefar dosimeter. Blood films were stained for unsegmented neutrophils before and after treatment with PAF on a placebo day.

RESULTS

Mean baseline total white cell counts and neutrophil counts did not differ on the two days. Mean baseline sGaw was significantly higher after inhaled salmeterol (1.84 (95% C1 1.45-2.23) s-1kPa-1) than after placebo (1.53 (1.24-1.82)). After placebo mean total white cell counts, neutrophil counts, and sGaw were reduced to 60 (43-78)%, 39 (14-64)%, and 82 (71-93)% of baseline respectively five minutes after inhaled PAF. After salmeterol treatment mean reductions five minutes after inhaled PAF were 59 (45-73)%, 40 (19-61)%, and 82 (71-93)% of baseline respectively. At 30 minutes after treatment with PAF the neutrophil count rebounded to 143 (82-204)% of baseline after placebo and to 127 (93-161)% after inhaled salmeterol. There was no significant difference in the percentage of immature neutrophils before and after treatment with PAF (2.0 (0.5-2.6)% compared with 3.9 (2.2-5.6)%.

CONCLUSIONS

Treatment with salmeterol did not inhibit reduction in total white cell count or neutrophil count, rebound neutrophilia, acute bronchoconstriction, or transient flushing after inhalation of PAF. These results conflict with the inhibitory effect of salmeterol on lung inflammation in guinea pigs but are consistent with the lack of effect of salbutamol in humans. Salmeterol does not have an anti-PAF effect in vivo in humans.

摘要

背景

血小板活化因子（PAF）是一种强效的炎症介质。吸入PAF可导致人体急性支气管收缩和白细胞计数短暂下降。沙美特罗可抑制豚鼠由PAF诱导的肺部炎症。

方法

在8名正常受试者中研究了沙美特罗对PAF诱导效应的影响，这些受试者在接受PAF激发前，每天两次吸入沙美特罗（50微克）或匹配的安慰剂，共一周。通过Mefar剂量计给予PAF（48微克）前后，从前臂导管采集血样以进行白细胞总数和中性粒细胞计数。在安慰剂日给予PAF治疗前后，对血涂片进行未分叶中性粒细胞染色。

结果

两天的平均基线白细胞总数和中性粒细胞计数无差异。吸入沙美特罗后的平均基线比气道传导率（sGaw）（1.84（95%可信区间1.45 - 2.23）s⁻¹kPa⁻¹）显著高于安慰剂组（1.53（1.24 - 1.82））。给予安慰剂后，吸入PAF五分钟后，平均白细胞总数、中性粒细胞计数和sGaw分别降至基线的60（43 - 78）%、39（14 - 64）%和82（71 - 93）%。沙美特罗治疗后，吸入PAF五分钟后的平均降低幅度分别为基线的59（45 - 73）%、40（19 - 61）%和82（71 - 93）%。PAF治疗30分钟后，安慰剂组中性粒细胞计数反弹至基线的143（82 - 204）%，吸入沙美特罗后为127（93 - 161）%。PAF治疗前后未成熟中性粒细胞的百分比无显著差异（2.0（0.5 - 2.6）%与3.9（2.2 - 5.6）%）。